Hin Hark Gan
My research is focused on 3D modeling of molecular interactions in the 3’-untranslated region (3’-UTR) of messenger RNAs (mRNAs). MicroRNAs (miRNAs) and RNA-binding proteins bind to sites in 3’UTRs, leading to the control of mRNA’s stability, localization and translation. Elucidating these interactions will advance our understanding of the mechanisms of key aspects of post-transcriptional regulation of gene expression.
Currently, my aim is to uncover the general rules of miRNA-target recognition, which is facilitated by effector proteins (e.g., Argonautes). Although miRNA-target recognition modes such as perfect and imperfect duplex associations are known, the role of Argonaute in these binding modes is not understood. Indeed, miRNA activity often cannot be accounted for using duplex-only considerations. Thus, one of my goals is to determine the binding interactions in the duplex-Argonaute complex that influence experimentally measured miRNA activity data. Our computational analysis includes predicting RNA 3D structures, computing binding free energies, and performing docking simulations. This 3D-based approach provides a more realistic modeling of the miRNA-induced silencing complex (miRISC) from which the rules of miRNA-target recognition should arise.